The proposed research is aimed at further defining the molecular mechanisms of the polymerization and gelation of deoxyhemoglobin S, exploration of the cellular determinants of red cell sickling and abnormalities of the red cell membrane in sickling disorders, attempts to modify and inhibit gelation, sickling and membrane damage, studies of the functional abnormalities of hemoglobin S-containing red cells, and studies of the intermolecular interactions of other mutant hemoglobins between each other and with hemoglobin S. Our approach will include studies of the gelation and polymer solubility of combinations of Hb S with other mutants and other proteins, measurements of the interrelations between various ligands of Hb on the respiratory functions and sickling properties of red cells containing Hb S, examination of covalent and non-covalent antisickling agents. We will continue to identify new hemoglobin mutants and investigate their structure-functional relations. BIBLIOGRAPHIC REFERENCES: Harrington, J.P., Elbaum, D., Bookchin, R.M., Wittenberg, J.B. and Nagel, R.L.: Ligand Kinetics of Hemoglobin S Containing Erythrocytes. Proc. Nat. Acad. Sci. 74:203, 1977. Landau, L.C., Nagel, R.L. and Bookchin, R.M.: Interrelated Effects of 2,3 DPG, H ion and CO2 on gelation of Hemoglobin S. Fed. Proc. 36:890, 1977 (Abstract).